Unit 7: Cannabis Flashcards
Cannabis
Cannabis:
- not a single drug, but a collection of drugs from the Cannabis sativa plant leaf
- commonly consumed through smoke inhalation
- highest concentration found in resin from female plant flowers
- hemp plants have no psychoactive properties
Psychoactive components:
1) delta-9 tetrahydrocannabinol (THC)
2) cannabidiol (CBD)
Cannabis Facts
Cannabis Facts:
- evidence suggests cannabis has been cultivated for over 12,000 years
- analgesic and anxiolytic properties
- believed to have originated in China and Mongolia; spread across Asia by 2000BC
- arrived in North America in the 19th century
Psychoactive Cannabis Effects
Effects of Psychoactive Cannabis
Mood
- euphoria OR dysphoria
- anxiolytic OR anxiogenic; depersonalization; aggravation of psychosis; paranoia (at high doses)
Sensory Perception
- heightened perception
- distortion of space and time
- misperceptions
- hallucinations
Arousal
- drowsiness
- sleep induction
- generalized CNS depressant
- additive effects with other depressants
Cognition
- global cognitive performance impairments
- memory impairment
- mental clouding
- fragmentation of thought
Motor Functioning
- increased motor activity followed by inertia (passivity) and ataxia (muscle incoordination)
- muscle weakness
- muscle twitching
Pain Sensation
- analgesia similar to codeine
Appetite
- increases appetite
Emesis
- low dose: antiemetic
- high dose/chronic use: emetic
Schizophrenia
- cannabis can exacerbate symptoms of schizophrenia
- increases risk of developing schizophrenia in people younger than 25
Cannabis Psychoactive Components
(THC and CBD)
(1) delta-9 tetrahydrocannabinol (THC)
Target: agonist of the CB1 and CB2 receptors
MOA: activates CB1 and CB2 receptors, influencing the firing rate of neurons
- complex effects; THC causes some neurons to fire more, and others to fire less
- disrupts various mental and physical processes
- influences [brain areas; (involved in)]:
- striatum; (pleasure/reward)
- basal ganglia; (motor control/planning)
- cerebellum; (coordination)
- hippocampus; (memory)
- amygdala; (mood)
- cortex; (cognition)
- hypothalamus; (appetite)
- brain stem/spinal cord; (pain, emesis)
(2) Cannabidiol (CBD)
Target: antagonist of CB1 and CB2 receptors
MOA:
- blocks CB1 and CB2 receptors
- agonist for serotonin receptor (5HT1A)
- agonist for GPR55 — orphan receptor (endogenous ligand unknown)
- CBD is thought to attenuate some of the negative effects of THC (eg: psychosis)
THC and CBD
Although these chemicals oppose each other in their actions, the combined effect is to activate the CB1 receptor
Cannabis Tolerance/Dependence/Addiction
Tolerance—occurs for most effects including “high” with chronic use
- downregulation of CB1 receptors
Dependence—long term and heavy use causes withdrawal symptoms:
- anxiety
- irritability
- GI disturbances
- loss of appetite
- insomnia
- approx. 9% of adult users will grow dependent; 17% for those who start in adolesence
Addiction
- previously not considered addictive
- cannabis use disorder and cannabis withdrawal are now included in DSM-V
- people who seek treatment have usually been smoking for 10+ years and have unsuccessfully tried quitting many times
- estimated that 30% of cannabis users may have some degree of cannabis use disorder; 10% likelihood of becoming addicted
Endocannabinoid System
Endocannabinoid System: active and complex signalling network made up of endocannabinoids (eCBs), important for regulating many functions, such as:
- eating — appetite stimulant
- cognition — promotes learning and memory
- growth and development — promotes bone formation
- pain — analgesic (descending pathway)
- anxiety
- reproduction
- metabolism
Analogy: think of the eCB system as the brain’s equalizer—modulating the intensity of every neuronal signal
Endocannabinoids
Endocannabinoids: endogenous cannabinoid neurotransmitter
Anandamide
- named after sanskrit word ananda (“bliss”)
- first discovered eCB—most abundant eCB is 2-AG
- when a presynaptic neuron is excessively firing and intensely activating its postsynaptic neuron, 2-AG is produced
- 2-AG activates CB1 receptors at the axon terminals of the presynaptic neuron
- CB1 receptor activation causes the presynaptic neuron to release less neurotransmitter
- quickly degraded — fast acting modulators to correct level of neurotransmission
- half life: 8-10 minutes
Cannabinoid Receptors
Cannabinoid Receptors
CB1
- most abundant G-protein coupled receptor in the brain
- located on axon terminals of neurons that release:
- glutamate
- GABA
- dopamine
- acetylcholine
- norepinephrine
- serotonin
- activated by:
- eCBs—modulatory brake; signals to presynaptic neuron to release less neurotransmitter
- THC—complex effects; can change the release of both excitatory AND inhibatory neurons
- widely expressed in the body—lungs, kidneys, pancrease and bones
CB2
- expressed in the brain at lower levels
- thought of as “peripheral cannabinoid receptors” since more highly expressed in the body than the brain
- notably found on immune cells
Phytocannabinoids
Phytocannabinoids: exogenous cannabinoid—derived from plants
delta-9 tetrahydrocannabidol (THC)
- long-lasting—acute effects last for hours, accumulates in fat tissues and remains in the body for weeks—half life: hours-days
- complex MOA — can change the release of both excitatory (eg: glutamate, dopamine) and inhibatory neurons (eg: GABA)
- appetite stimulant
- anti-emetic
- analgesic
- reduces muscle spasticity
- impairs learning and memory
- hallucinations (sensory and time distortion)
- can induce schizophrenia in users >25 and psychosis
Cannabidiol (CBD)
- does not elicit euphoria/”high”
- analgesic properties
- anti-epileptic
- anti-psychotic
- anti-cancer
Cannabis and Psychosis
Longitudinal study in NZ (Arsenault et al. 2002)
Participants: children at age 11, 15, 18, and 26
Findings:
(1) Psychosis
- cannabis use is associated with an increased risk of experiencing symptoms of schizophrenia, even after psychotic symptoms preceding the onset of cannabis use are controlled for
- this indicates that cannabis use is not secondary to a pre-existing psychosis
(2) Schizophrenia
- early cannabis use (by age 15) confers greater risk for schizophrenia outcomes than later use (by age 18)
- the youngest users may be most at risk bc their use becomes longstanding
(3) Depression
- risk was specific to cannabis use, as opposed to use of other drugs, and early cannabis use did not predict later depression
Medical Uses of Cannabis
Cannabinoid Drugs
(1) Nabiximol (“Sativex”) — 1:1 THC:CBD (2.7 mg : 2.4 mg)
- oral spray
- reduces muscle spasticity and alleviates neuropathic pain in patients with multiple sclerosis (MS)
- reduces pain in cancer patients
(2) Cannabidiol (“Epidiolex”) — CBD
- injested (oral solution) or inhaled (nasal spray)
- approved to treat childhood epilepsy
- CBD is being tested for treatment of chronic pain and inflammatory disorders
(3) Dronabinol (“Marinol”) — THC capsule
- approved to treat anorexia in HIV/AIDS patients
- manages nausea and vomiting induced by chemotherapy
(4) Nabilone
- synthetic cannabinoid, analog of THC
- approved for same uses as (3) Dronabinol
- off-label treatment for chronic pain/neuropathic pain and fibromyalgia
Non-cannabinoid
Rimonabant
- MOA: CB1 receptor antagonist
-opposite effect of CB1R agonists (ie: reduces appetite)
- approved in EU in 2005 as a weight loss drug
- HOWEVER, also causes suicidal ideation—discontinued in 2008
Cannabinoid Derivative
Cannabinoid Derivative
“Spice/K2”
- synthetic cannabinoid, immitating psychoactive properties of THC
- “designer drug”
- sprayed onto leaves and smoked like cannabis
- adverse effects:
- heart palpitations
- anxiety; paranoia
- emesis
- confusion
- poor coordination
- seizures
- psychosis
- hallucinations
- violent acts
- increased rates of suicide
- most notably, Spice causes catatonia — a loss of temporal and spatial awareness
- with repeated ingestion, a user could spend hours or even days in this drug-induced catatonic state—feeling as though only minutes have passed
